Chemistry:Lysergine

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Lysergine, also known as 9,10-didehydro-6,8β-dimethylergoline, is an ergot alkaloid and serotonin receptor agonist of the ergoline family.[1][2][3] It is a minor constituent of ergot.[1]

Pharmacology

Lysergine shows selectivity for activation of the serotonin 5-HT2A receptor over several other closely related serotonin receptors (54-fold over the 5-HT2B receptor, 38-fold over the 5-HT2C receptor, and 127-fold over the 5-HT1A receptor).[2][3] The drug is a partial agonist of the 5-HT2A receptor with moderate intrinsic activity (Emax = 57%).[2][3]

Lysergine activation of serotonin receptors[2][3]
5-HT1A 5-HT2A 5-HT2B 5-HT2C
EC50 Emax EC50 Emax EC50 Emax EC50 Emax
342 ± 23 ND 2.7 ± 1.6 57% 145 ± 54 36% 103 ± 9 42%
Notes: EC50 values are nanomolar (nM) and EC50 values are mean ± SEM.[2][3]

An analogue of lysergine, (+)-13-fluorolysergol, is an even more selective agonist of the 5-HT2A receptor than lysergine (EC50 for 5-HT2B and 5-HT2C of >10,000 nM).[2][3] However, this compound has relatively weak maximal efficacy in activating the receptor (Emax = 17%).[2][3]

Chemistry

Analogues

Isotryptamine or JRT-type analogues of lysergine have been described.[4][5]

See also

References

  1. ↑ 1.0 1.1 "Bioconversions of ergot alkaloids". Advances in Biochemical Engineering/Biotechnology 44: 123–144. 1991. doi:10.1007/Bfb0000750. ISBN 978-3-540-54094-6. PMID 1781317. 
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 "Serotonin 2A Receptor (5-HT2AR) Agonists: Psychedelics and Non-Hallucinogenic Analogues as Emerging Antidepressants". Chemical Reviews 124 (1): 124–163. January 2024. doi:10.1021/acs.chemrev.3c00375. PMID 38033123. 
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 "Synthesis of (+)-Lysergol and Its Analogues To Assess Serotonin Receptor Activity". Organic Letters 19 (3): 624–627. February 2017. doi:10.1021/acs.orglett.6b03779. PMID 28106398. 
  4. ↑ "Novel Desamide Isotryptamine Tetracycles as 5‑HT2C Agonists for Treating Brain Disorders". ACS Medicinal Chemistry Letters 16 (6): 976–977. June 2025. doi:10.1021/acsmedchemlett.5c00286. PMID 40529093. 
  5. ↑ Tuck JR, Olson DE, Basargin AG, Dunlap L, Powell NA, Chytil M, Ghosh M, "Desamide isotryptamine tetracycles for treating brain disorders", WO patent 2025080608, published 17 April 2025, assigned to Delix Therapeutics Incand University of California




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